The specific aims of this research are: 1) to investigate effects of dietary modifications and endocrine treatments on the metabolism of branched-chain amino and ketoacids in the intact animal and in an isolated perfused preparation representative of muscle (eviscerated rat hindquarter); 2) to determine how the various treatments modify the activities of enzymes for the degradation of the branched-chain amino acids in different tissues and organs; 3) to extend knowledge of interorgan relationships in the metabolisms of branched-chain amino acids by studying the metabolic fate of these amino acids in the isolated perfused kidney. Effects of altering dietary protein content, of diabetes and of glucocorticoid treatment on transamination and oxidation of branched-chain amino acids and on blood and tissue amino acid patterns will be measured in the various preparations in order to detect associations between changes in enzyme activity and changes in the flux of branched-chain amino acids and their products through different metabolic pathways. Effects of specific treatments, such as, feeding branched-chain amino or ketoacids and feeding discrete meals, that are known to influence the activity of the dehydrogenase, on rates of oxidation of branched-chain amino acids and on their incorporation into tissues will be studied in order to extend information about the nature of leucine-isoleucine and valine antagonisms. This research studies of effects of dietary and endocrine treatments on amino acid metabolism in vivo. The long-term objective is to enlarge the base of knowledge about branched-chain amino acid metabolism in the intact organism in relation to conditions in which altered metabolism of these amino acids may have clinical implications. These include liver failure, in which altered blood branched-chain amino acid concentrations appear to affect brain neurotransmitter concentrations and mental acitivty; trauma, in which adminstration of branched-chain amino acids appear to reduce nitrogen loss; renal disease and urea cycle defects, in which branched-chain keto acid administration appears to improve nitrogen utilization; diabetes and long-term fasting or starvation.